Search results for: financial risk tolerance

Authors: Nawaporn Thongnut

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The objective was to study the process and how to prepare the accounting of the Thai temples and to study the performance and quality in the accounting preparation of the temples in accordance with the regulation. The population was the accountants and individuals involved in the accounting preparation of 17 temples in the suburban Bangkok. The measurement used in this study was questionnaire. The statistics used in the analysis are the descriptive statistic. The data was presented in the form of percentage tables to describe the data on the demographic characteristics. The study found that temple wardens were responsible for the accounting and reporting of the temples. Abbots were to check the accuracy of the accounts in the monasteries. Mostly, there was no account auditing of the monasteries from the outside. The practice when receiving income for most of the monasteries had been keeping financial document in an orderly manner.

Keywords: corporate social responsibility, creating shared value, management accountant’s roles, stock exchange of Thailand

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Authors: Somayeh Nezami

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The management of financial and human resources of police in metropolitans requires many information and exact plans to reduce a rate of crime and increase the safety of the society. Geographical Information Systems have an important role in providing crime maps and their analysis. By using them and identification of crime hot spots along with spatial presentation of the results, it is possible to allocate optimum resources while presenting effective methods for decision making and preventive solutions. In this paper, we try to explain and compare between some of the methods of hot spots analysis such as Mode, Fuzzy Mode and Nearest Neighbour Hierarchical spatial clustering (NNH). Then the spots with the highest crime rates of drug smuggling for one province in Iran with borderline with Afghanistan are obtained. We will show that among these three methods NNH leads to the best result.

Keywords: GIS, Hot spots, nearest neighbor hierarchical spatial clustering, NNH, spatial analysis of crime

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Authors: Wajad Nazeer, Saghir Ahmad, Khalid Mahmood, Altaf Hussain, Abid Mahmood, Baoliang Zhou

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MNH-886(Bt.) is a upland cotton cultivar (Gossypium hirsutum L.) developed through hybridization of three parents [(FH-207×MNH-770)×Bollgard-1] at Cotton Research Station Multan, Pakistan. It is resistant to CLCuVD with 16.25 % disease incidence (60 DAS, March sowing) whereas moderately susceptible to CLCuVD when planted in June with disease incidence 34 % (60 DAS). This disease reaction was lowest among 25 cotton advanced lines/varieties tested at hot spots of CLCuVD. Its performance was tested during 2009 to 2012 in various indigenous, provincial, and national varietal trials in comparison with the commercial variety IR-3701 and AA-802 & CIM-496. In PCCT trial during 2009-10; 2011-12, MNH-886 surpassed all the existing Bt. strains along with commercial varieties across the Punjab province with seed cotton yield production 2658 kg ha-1 and 2848 kg ha-1 which was 81.31 and 13% higher than checks, respectively. In National Coordinated Bt. Trial, MNH-886(Bt.) produced 3347 kg ha-1 seed cotton at CCRI, Multan; the hot spot of CLCuVD, in comparison to IR-3701 which gave 2556 kg ha-1. It possesses higher lint percentage (41.01%), along with the most desirable fibre traits (staple length 28.210mm, micronaire value 4.95 µg inch-1 and fibre strength 99.5 tppsi, and uniformity ratio 82.0%). The quantification of toxicity level of crystal protein was found positive for Cry1Ab/Ac protein with toxicity level 2.76µg g-1 and Mon 531 event was confirmed. Having tremendous yield potential, good fibre traits, and great tolerance to CLCuVD we can recommended this variety for cultivation in CLCuVD hotspots of Pakistan.

Keywords: cotton, cultivar, cotton leaf curl virus, CLCuVD hit districts

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Authors: Eftychia Pappa, Heleni Vastardis, Christos Rahiotis, Andriani Vazaiou

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The aim of this study was to evaluate the prevalence of dry-mouth symptoms (xerostomia) and compare it with alterations in salivary characteristics of children and adolescents with type 1 diabetes (DM1), as measured with the use of chair-side saliva tests. This study also investigated the possible association between salivary dysfunction and incidence of caries, in relation to the level of metabolic control. A cross-sectional study was performed on young patients (6-18 years old) allocated among 3 groups: 40 patients poorly-controlled (DM1-A, HbA1c>8%), 40 well-controlled (DM1-B, HbA1c≤8%) and 40 age- and sex-matched healthy controls. The study was approved by the Research Ethics Committee of University of Athens and the parents signed written informed consent. All subjects were examined for dental caries, oral hygiene and salivary factors. Assessments of salivary function included self-reported xerostomia, quantification of resting and stimulated whole saliva flow rates, pH values, buffering capacity and saliva’s viscosity. Salivary characteristics were evaluated with the use of GC Saliva Check Buffer (3Μ ESPE). Data were analysed by chi-square and Kruskal-Wallis tests. Subjects with diabetes reported xerostomia more frequently than healthy controls (p<0.05). Unstimulated salivary flow rate and pH values remained significantly lower in DM1-A compared to DM1-B and controls. Low values of resting salivary flow rate were associated with a higher prevalence of dental caries in children and adolescents with poorly-controlled DM1 (p<0.05). The results suggested that diabetes-induced alterations in salivary characteristics are indicative of higher caries susceptibility of diabetics and chair-side saliva tests are a useful tool for the evaluation of caries risk assessment.

Keywords: caries risk assessment, saliva diagnostic tests, type 1 diabetes, xerostomia

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Authors: Manpreet Kaur

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When legitimate credit card users are mistakenly labelled as fraudulent in numerous financial delated applications, there are numerous ethical problems. The innovative machine learning approach we have suggested in this research outperforms the current models and shows how to model a data set for credit card fraud detection while minimizing false positives. As a result, we advise using random forests as the best machine learning method for predicting and identifying credit card transaction fraud. The majority of victims of these fraudulent transactions were discovered to be credit card users over the age of 60, with a higher percentage of fraudulent transactions taking place between the specific hours.

Keywords: automated fraud detection, isolation forest method, local outlier factor, ML algorithm, credit card

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Authors: Xiaomin Zhong, Alexander Pate, Ya-Ting Yang, Ali Fahmi, Darren M. Ashcroft, Ben Goldacre, Brian Mackenna, Amir Mehrkar, Sebastian C. J. Bacon, Jon Massey, Louis Fisher, Peter Inglesby, Kieran Hand, Tjeerd van Staa, Victoria Palin

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Background: This study aimed to predict risks of potentially inappropriate antibiotic type and repeat prescribing and assess changes during COVID-19. Methods: With the approval of NHS England, we used the OpenSAFELY platform to access the TPP SystmOne electronic health record (EHR) system and selected patients prescribed antibiotics from 2019 to 2021. Multinomial logistic regression models predicted the patient’s probability of receiving an inappropriate antibiotic type or repeating the antibiotic course for each common infection. Findings: The population included 9.1 million patients with 29.2 million antibiotic prescriptions. 29.1% of prescriptions were identified as repeat prescribing. Those with same-day incident infection coded in the EHR had considerably lower rates of repeat prescribing (18.0%), and 8.6% had a potentially inappropriate type. No major changes in the rates of repeat antibiotic prescribing during COVID-19 were found. In the ten risk prediction models, good levels of calibration and moderate levels of discrimination were found. Important predictors included age, prior antibiotic prescribing, and region. Patients varied in their predicted risks. For sore throat, the range from 2.5 to 97.5th percentile was 2.7 to 23.5% (inappropriate type) and 6.0 to 27.2% (repeat prescription). For otitis externa, these numbers were 25.9 to 63.9% and 8.5 to 37.1%, respectively. Interpretation: Our study found no evidence of changes in the level of inappropriate or repeat antibiotic prescribing after the start of COVID-19. Repeat antibiotic prescribing was frequent and varied according to regional and patient characteristics. There is a need for treatment guidelines to be developed around antibiotic failure and clinicians provided with individualised patient information.

Keywords: antibiotics, infection, COVID-19 pandemic, antibiotic stewardship, primary care

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Authors: Renato Figueira Franco

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This paper aims to create a representational information system applied to the securities market, particularly the development of an ontology applied to the analysis of the Key Information Documents of Contracts for Difference. The process of obtaining knowledge and its proper formal representation has raised the attention both from the scientific literature and the capital markets supervisory authorities. The formal knowledge representation is embodied in the construction of ontologies, which are responsible for defining a knowledge base structure of a given scientific domain, facilitating its understanding, and allowing its sharing among the scientific community. The scope of this study is restricted to the analysis of capital markets ontologies in order to capture its structure, semantics and knowledge sharing between people and systems.

Keywords: ontology, financial markets, CFD, PRIIPs, key information documents

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Authors: Alejandro Arnaldo Barroso Martinez

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Unlike sex, which is constituted by anatomic-physiological differences, gender is a social construction. Our thoughts and behaviors as females and males are not etched in stone by our biology but rather from how society expects us to think and behave based on our sex assignment in the womb. Social expectations, values, and roles are taken on by individuals and shape the ways considered acceptable and linked to our bodies, feelings, and interpersonal relationships. Furthermore, these evolve into dire consequences for those who do not meet these disciplinary, economic, and cultural standards. Then, the social learning of gender identity implies the individual’s psychological sense of being, and it might be highly linked to a sense of life and suicide attempts. As a result, suicide has been considered a gender issue with differences in the rates and means used by men and women worldwide. Nevertheless, there has been a misunderstanding of the meaning of being male or female in a particular context and how it becomes a risk process for suicide attempts. For this reason, the general objective of the current research is to explain how this process occurs in Cuba. From a Critical Sociology and Social Psychology, a qualitative methodology was developed through six case studies and qualitative in-depth interviews. The analysis is focused on the sequence and interplay between two dimensions of meaning: signifiers and voices. Findings show that the risk process of suicide attempts in Cuba means some patriarchal beliefs and practices as part of informal educational models and some positivist practices in mental health attention. Findings also show that community relations create a sense of belonging, and it is a protection against suicide attempts in Cuba. Those frames of signifiers and voices explain in both males and females but differently when and how they are suffering from isolation, violence, the normalization of emotional awareness, and emotional distress expression. Suicide prevention programs should take gender learning into account as a cultural process.

Keywords: social constructions, gender identity, meanings, suicide attempt

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Authors: F. Christie, M. Staber

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Malnutrition is a predictor of poor clinical outcome in the elderly. Up to 60% of hip fracture patients are clinically malnourished on admission. This study assessed the perioperative nutritional state of patients admitted with a proximal femoral fracture and examined if adequate nutritional support was achieved. Methods: Prospective, the observational audit of 30 patients, admitted with a proximal femoral fracture, over a one-month period. We recorded: patient demographics; surgical delay; nutritional state on admission; documentation of Malnutrition Universal Screening Tool (MUST) score; dietician input and daily calorie intake through food charts. The nutritional state was re-assessed weekly and at discharge. The outcome was measured by the length of hospital stay and thirty-day mortality. Results: Mean age 87, M:F 1:2 and all patients were ASA three or four. Five patients (17%) had a prolonged ( >24 hours) fasting period. All patients had a MUST score completed on admission, 27% were underweight and 30% were high risk for malnutrition. Twenty-six patients (87%) were appropriately assessed for dietician referral. Thirteen patients had food charts; on average, hospital meals provided 1500kcal daily. No patient achieved > 75% of the provided calories with 69% of patients achieving 50% or less. Only three patients were started on nutritional supplements. Twenty-three patients (77%) lost weight, averaging 6% weight loss during admission. Mean length of stay (LOS) was 23 days and 30-day mortality 9%. Four patients (13%) gained weight, their mean LOS was 17 days and 30-day mortality 0%. Discussion: Malnutrition in the elderly originates in the community. Following major trauma it’s difficult to reverse nutritional deficits in hospitals. It’s therefore concerning that no high-risk patient achieved their recommended calorie intake. Perioperative optimisation needs to include early nutritional intervention, early anaesthetic review and adjusted anaesthetic techniques to support feeding.

Keywords: trauma, nutrition, neck of femur fracture

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Authors: Sherif Sabri, Suzy Fawzi, Sanaa Abdelshafy, Ayman Nagah

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Introduction: Static derangements in lactate homeostasis during ICU stay have become established as a clinically useful marker of increased risk of hospital and ICU mortality. Lactate indices or kinetic alteration of the anaerobic metabolism make it a potential parameter to evaluate disease severity and intervention adequacy. This is an inexpensive and simple clinical parameter that can be obtained by a minimally invasive means. Aim of work: Comparing the predictive value of dynamic indices of hyperlactatemia in the first twenty four hours of intensive care unit (ICU) admission with other static values are more commonly used. Patients and Methods: This study included 40 critically ill patients above 18 years old of both sexes with Hyperlactamia (≥ 2 m mol/L). Patients were divided into septic group (n=20) and low oxygen transport group (n=20), which include all causes of low-O2. Six lactate indices specifically relating to the first 24 hours of ICU admission were considered, three static indices and three dynamic indices. Results: There were no statistically significant differences among the two groups regarding age, most of the laboratory results including ABG and the need for mechanical ventilation. Admission lactate was significantly higher in low-oxygen transport group than the septic group [37.5±11.4 versus 30.6±7.8 P-value 0.034]. Maximum lactate was significantly higher in low-oxygen transport group than the septic group P-value (0.044). On the other hand absolute lactate (mg) was higher in septic group P-value (< 0.001). Percentage change of lactate was higher in the septic group (47.8±11.3) than the low-oxygen transport group (26.1±12.6) with highly significant P-value (< 0.001). Lastly, time weighted lactate was higher in the low-oxygen transport group (1.72±0.81) than the septic group (1.05±0.8) with significant P-value (0.012). There were statistically significant differences regarding lactate indices in survivors and non survivors, whether in septic or low-oxygen transport group. Conclusion: In critically ill patients, time weighted lactate and percent in lactate change in the first 24 hours can be an independent predictive factor in ICU mortality. Also, a rising compared to a falling blood lactate concentration over the first 24 hours can be associated with significant increase in the risk of mortality.

Keywords: critically ill patients, lactate indices, mortality in intensive care, anaerobic metabolism

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Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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Authors: Dipendra Kumar Yadav, Nabaraj Paudel, Anjana Yadav

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Background: Low Birth weight (LBW) is defined as the weight at birth less than 2500 grams, irrespective of the period of their gestation. LBW is an important indicator of general health status of population and is considered as the single most important predictors of infant mortality especially of deaths within the first month of life that is birth weight determines the chances of newborn survival. Objective of this study was to identify the maternal risk factors associated with low birth weight neonates. Materials and Methods: A hospital based case-control study was conducted in maternity ward of Manipal Teaching Hospital, Pokhara, Nepal from 23 September 2014 to 12 November 2014. During study period 59 cases were obtained and twice number of control group were selected with frequency matching of the mother`s age with ± 3 years and total controls were 118. Interview schedule was used for data collection along with record review. Data were entered in Epi-data program and analysis was done with help of SPSS software program. Results: From bivariate logistic regression analysis, eighteen variables were found significantly associated with LBW and these were place of residence, family monthly income, education, previous still birth, previous LBW, history of STD, history of vaginal bleeding, anemia, ANC visits, less than four ANC visits, de-worming status, counseling during pregnancy, CVD, physical workload, stress, extra meal during pregnancy, smoking and alcohol consumption status. However after adjusting confounding variables, only six variables were found significantly associated with LBW. Mothers who had family monthly income up to ten thousand rupees were 4.83 times more likely to deliver LBW with CI (1.5-40.645) and p value 0.014 compared to mothers whose family income NRs.20,001-60,000. Mothers who had previous still birth were 2.01 times more likely to deliver LBW with CI (0.69-5.87) and p value 0.02 compared to mothers who did not has previous still birth. Mothers who had previous LBW were 5.472 times more likely to deliver LBW with CI (1.2-24.93) and p value 0.028 compared to mothers who did not has previous LBW. Mothers who had anemia during pregnancy were 3.36 times more likely to deliver LBW with CI (0.77-14.57) and p value 0.014 compared to mothers who did not has anemia. Mothers who delivered female newborn were 2.96 times more likely to have LBW with 95% CI (1.27-7.28) and p value 0.01 compared to mothers who deliver male newborn. Mothers who did not get extra meal during pregnancy were 6.04 times more likely to deliver LBW with CI (1.11-32.7) and p value 0.037 compared to mothers who getting the extra meal during pregnancy. Mothers who consumed alcohol during pregnancy were 4.83 times more likely to deliver LBW with CI (1.57-14.83) and p value 0.006 compared to mothers who did not consumed alcohol during pregnancy. Conclusions: To reduce low birth weight baby through economic empowerment of family and individual women. Prevention and control of anemia during pregnancy is one of the another strategy to control the LBW baby and mothers should take full dose of iron supplements with screening of haemoglobin level. Extra nutritional food should be provided to women during pregnancy. Health promotion program will be focused on avoidance of alcohol and strengthen of health services that leads increasing use of maternity services.

Keywords: low birth weight, case-control, risk factors, hospital based study

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Authors: Mahsa Tavakoli, Seyed Mohammad Hojjati, Yahya Kooch

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In this study, the effect of coal mining activities on lead and cadmium concentrations and distribution in soil was investigated in Hyrcanian forest, North Iran. 16 plots (20×20 m²) were established by systematic-randomly (60×60 m²) in an area of 4 ha (200×200 m²-mine entrance placed at center). An area adjacent to the mine was not affected by the mining activity; considered as the controlled area. In order to investigate soil lead and cadmium concentration, one sample was taken from the 0-10 cm in each plot. To study the spatial pattern of soil properties and lead and cadmium concentrations in the mining area, an area of 80×80m² (the mine as the center) was considered and 80 soil samples were systematic-randomly taken (10 m intervals). Geostatistical analysis was performed via Kriging method and GS⁺ software (version 5.1). In order to estimate the impact of coal mining activities on soil quality, pollution index was measured. Lead and cadmium concentrations were significantly higher in mine area (Pb: 10.97±0.30, Cd: 184.47±6.26 mg.kg^-1) in comparison to control area (Pb: 9.42±0.17, Cd: 131.71±15.77 mg.kg^-1). The mean values of the PI index indicate that Pb (1.16) and Cd (1.77) presented slightly polluted. Results of the NIPI index showed that Pb (1.44) and Cd (2.52) presented slight pollution and moderate pollution respectively. Results of variography and kriging method showed that it is possible to prepare interpolation maps of lead and cadmium around the mining areas in Hyrcanian forest. According to results of pollution and risk assessments, forest soil was contaminated by heavy metals (lead and cadmium); therefore, using reclamation and remediation techniques in these areas is necessary.

Keywords: traditional coal mining, heavy metals, pollution indicators, geostatistics, Caspian forest

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Authors: Reeta Devi, Hitender Kumar Tyagi, Dinesh Kumar

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In present scenario, cardiovascular problems are growing challenge for researchers and physiologists. As heart disease have no geographic, gender or socioeconomic specific reasons; detecting cardiac irregularities at early stage followed by quick and correct treatment is very important. Electrocardiogram is the finest tool for continuous monitoring of heart activity. Heart rate variability (HRV) is used to measure naturally occurring oscillations between consecutive cardiac cycles. Analysis of this variability is carried out using time domain, frequency domain and non-linear parameters. This paper presents HRV analysis of the online dataset for normal sinus rhythm (taken as healthy subject) and sudden cardiac death (SCD subject) using all three methods computing values for parameters like standard deviation of node to node intervals (SDNN), square root of mean of the sequences of difference between adjacent RR intervals (RMSSD), mean of R to R intervals (mean RR) in time domain, very low-frequency (VLF), low-frequency (LF), high frequency (HF) and ratio of low to high frequency (LF/HF ratio) in frequency domain and Poincare plot for non linear analysis. To differentiate HRV of healthy subject from subject died with SCD, k –nearest neighbor (k-NN) classifier has been used because of its high accuracy. Results show highly reduced values for all stated parameters for SCD subjects as compared to healthy ones. As the dataset used for SCD patients is recording of their ECG signal one hour prior to their death, it is therefore, verified with an accuracy of 95% that proposed algorithm can identify mortality risk of a patient one hour before its death. The identification of a patient’s mortality risk at such an early stage may prevent him/her meeting sudden death if in-time and right treatment is given by the doctor.

Keywords: early stage prediction, heart rate variability, linear and non-linear analysis, sudden cardiac death

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Authors: Yasir M. Alyazichi, Brian G. Jones, Errol McLean, Hamd N. Altalyan, Ali K. M. Al-Nasrawi

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The main purpose of this study is to assess the sediment quality and potential ecological risk in marine sediments in Gymea Bay located in south Sydney, Australia. A total of 32 surface sediment samples were collected from the bay. Current track trajectories and velocities have also been measured in the bay. The resultant trace elements were compared with the adverse biological effect values Effect Range Low (ERL) and Effect Range Median (ERM) classifications. The results indicate that the average values of chromium, arsenic, copper, zinc, and lead in surface sediments all reveal low pollution levels and are below ERL and ERM values. The highest concentrations of trace elements were found close to discharge points and in the inner bay, and were linked with high percentages of clay minerals, pyrite and organic matter, which can play a significant role in trapping and accumulating these elements. The lowest concentrations of trace elements were found to be on the shoreline of the bay, which contained high percentages of sand fractions. It is postulated that the fine particles and trace elements are disturbed by currents and tides, then transported and deposited in deeper areas. The current track velocities recorded in Gymea Bay had the capability to transport fine particles and trace element pollution within the bay. As a result, hydrodynamic measurements were able to provide useful information and to help explain the distribution of sedimentary particles and geochemical properties. This may lead to knowledge transfer to other bay systems, including those in remote areas. These activities can be conducted at a low cost, and are therefore also transferrable to developing countries. The advent of portable instruments to measure trace elements in the field has also contributed to the development of these lower cost and easily applied methodologies available for use in remote locations and low-cost economies.

Keywords: current track velocities, gymea bay, surface sediments, trace elements

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Authors: Gary J. Pickering, Sarah Lucas, Catherine E. Klodnicki, Nicole J. Gaudette

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Two taste pheno types that are of interest in the study of habitual diet-related risk factors and disease are 6-n-propylthiouracil (PROP) responsiveness and thermal tasting. Individuals differ considerable in how intensely they experience the bitterness of PROP, which is partially explained by three major single nucleotide polymorphisms associated with the TAS2R38 gene. Importantly, this variable responsiveness is a useful proxy for general taste responsiveness, and links to diet-related disease risk, including body mass index, in some studies. Thermal tasting - a newly discovered taste phenotype independent of PROP responsiveness - refers to the capacity of many individuals to perceive phantom tastes in response to lingual thermal stimulation, and is linked with TRPM5 channels. Thermal tasters (TTs) also experience oral sensations more intensely than thermal non-tasters (TnTs), and this was shown to associate with differences in self-reported food preferences in a previous survey from our lab. Here we report on two related studies, where we sought to determine whether PROP responsiveness and thermal tasting would associate with perceptual differences in the oral sensations elicited by sampled energy-dense foods, and whether in turn this would influence liking. We hypothesized that hyper-tasters (thermal tasters and individuals who experience PROP intensely) would (a) rate sweet and high-fat foods more intensely than hypo-tasters, and (b) would differ from hypo-tasters in liking scores. (Liking has been proposed recently as a more accurate measure of actual food consumption). In Study 1, a range of energy-dense foods and beverages, including table cream and chocolate, was assessed by 25 TTs and 19 TnTs. Ratings of oral sensation intensity and overall liking were obtained using gVAS and gDOL scales, respectively. TTs and TnTs did not differ significantly in intensity ratings for most stimuli (ANOVA). In a 2nd study, 44 female participants sampled 22 foods and beverages, assessing them for intensity of oral sensations (gVAS) and overall liking (9-point hedonic scale). TTs (n=23) rated their overall liking of creaminess and milk products lower than did TnTs (n=21), and liked milk chocolate less. PROP responsiveness was negatively correlated with liking of food and beverages belonging to the sweet or sensory food grouping. No other differences in intensity or liking scores between hyper- and hypo-tasters were found. Taken overall, our results are somewhat unexpected, lending only modest support to the hypothesis that these taste phenotypes associate with energy-dense food liking and consumption through differences in the oral sensations they elicit. Reasons for this lack of concordance with expectations and some prior literature are discussed, and suggestions for future research are advanced.

Keywords: taste phenotypes, sensory evaluation, PROP, thermal tasting, diet-related health risk

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Authors: Yifan Lu, Ying Cui, Ying Zhu, Edward S. Lu, Rebecca Zeng, Rohan Bajaj, Raviv Katz, Rongrong Le, Jay C. Wang, John B. Miller

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Purpose: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcome and is associated with an increased risk of cerebral stroke and cardiovascular events. Fluorescein angiography (FA) is the traditional diagnostic tool for RAO; however, wide-field swept-source optical coherence tomography angiography (WF SS-OCTA), as a nascent imaging technology, is able to provide quick and non-invasive angiographic information with a wide field of view. In this study, we looked for associations between OCT-A vascular metrics and visual acuity in patients with prior diagnosis of RAO. Methods: Patients with diagnoses of central retinal artery occlusion (CRAO) or branched retinal artery occlusion (BRAO) were included. A 6mm x 6mm Angio and a 15mm x 15mm AngioPlex Montage OCT-A image were obtained for both eyes in each patient using the Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm x 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. The average measurement of the central foveal subfield, inner ring, and outer ring was calculated for each parameter. Non-perfusion area (NPA) was manually measured using 15mm x 15mm Montage images. A linear regression model was utilized to identify a correlation between the imaging metrics and visual acuity. A P-value less than 0.05 was considered to be statistically significant. Results: Twenty-five subjects were included in the study. For RAO eyes, there was a statistically significant negative correlation between vision and retinal thickness as well as superficial capillary plexus vessel density (SCP VD). A negative correlation was found between vision and deep capillary plexus vessel density (DCP VD) without statistical significance. There was a positive correlation between vision and choroidal thickness as well as choroidal volume without statistical significance. No statistically significant correlation was found between vision and the above metrics in contralateral eyes. For NPA measurements, no significant correlation was found between vision and NPA. Conclusions: This is the first study to our best knowledge to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between various retinal vascular imaging metrics and visual outcomes. Further investigations should explore the associations between these imaging findings and cardiovascular risk as RAO patients are at elevated risk for symptomatic stroke. The results of this study provide a basis to understand the structural changes involved in visual outcomes in RAO. Furthermore, they may help guide management of RAO and prevention of cerebral stroke and cardiovascular accidents in patients with RAO.

Keywords: OCTA, swept-source OCT, retinal artery occlusion, Zeiss Plex Elite

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Authors: Muhammad Iqbal, Hafiz Muhammad Tauqeer, Hamza Rafaqat, Muhammad Naveed, Muhammad Awais Irshad

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Soil pollution with chromium (Cr) has become one of the most important concerns due to its toxicity for humans. To date, various remediation approaches have been employed for the remediation and management of Cr contaminated soils. Phytoextraction is an eco-friendly and emerging remediation approach which has gained attention due to several advantages over conventional remediation approach. The use of energy crops for phytoremediation is an emerging trend worldwide. These energy crops have high tolerance against various environmental stresses, the potential to grow in diverse ecosystems and high biomass production make them a suitable candidate for phytoremediation of contaminated soils. The removal efficiency of plants in phytoextraction depends upon several soil and plant factors including solubility, bioavailability and metal speciation in soils. A pot scale experiment was conducted to evaluate the phytoextraction potential of Arundo donax L. with the application of acetic acid (A.A) in Cr contaminated soils. Plants were grown in pots filled with 5 kg soils for 90 days. After 30 days plants acclimatization in pot conditions, plants were treated with various levels of Cr (2.5 mM, 5 mM, 7.5 mM, 10 mM) and A.A (Cr 2.5 mM + A.A 2.5 mM, Cr 5 mM + A.A 2.5 mM, Cr 7.5 mM + A.A 2.5 mM, Cr 10 mM + A.A 2.5 mM). The application of A.A significantly increased metal uptake and in roots and shoots of A. donax. This increase was observed at Cr 7.5 mM + A.A 2.5 mM but at high concentrations, visual symptoms of Cr toxicity were observed on leaves. Similarly, A.A applications also affect the activities of key enzymes including catalase (CAT), superoxidase dismutase (SOD), and ascorbate peroxidase (APX) in leaves of A. donax. Based on results it is concluded that the applications of A.A acid for phytoextraction is an alternative approach for the management of Cr affected soils and synthetic chelators should be replaced with organic acids.

Keywords: acetic acid, A. donax, chromium, energy crop, phytoextraction

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Authors: Taddese Alemu Zerfu, Melaku Umeta Deressa, Kaleab Baye

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Background: Maternal and child under-nutrition is the underlying cause of 3•5 million annual deaths, globally. Anemia during pregnancy is among the leading nutritional disorders with serious short and long term consequences to both the mother and fetus. Objective: Examine the effect of dietary diversity on maternal anemia, nutritional status and key pregnancy outcomes of pregnancy. Methods: A prospective cohort study design, involving a total of 432 eligible pregnant women, in their second antenatal care visit was conducted between August 2014 to March, 2015. The individual dietary diversity status of mothers was used as the exposure variable to select, enroll and follow the mothers. All mothers were enrolled during second antenatal care visit and followed until delivery. Epi-data, SPSS and STATA software are used to enter and analyze the data. Chi-square test, independent 't'-test, and GLM are used to calculate risk, association and differences between key variables at P < 0.05. Results: Study participants did not differ in many of the basic characteristics (p < 0.05). The incidence of maternal anemia increased significantly from 28.6% to 32.1% between baseline and term. Pregnant mothers with inadequate dietary diversity groups had more (56% at baseline and 68% at term) risk of anemia than the comparison (adequate) groups, (RR, 1.56 and 1.68; 95% CI, 1.24 - 1.83 and 1.39 - 2.04). The overall incidence of still birth, low birth weight and pre-term birth was 4.5%, 9.1% and 13.6%, respectively. The variation of these outcomes was significant across study groups (P < 0.05). Conclusion and recommendations: Dietary diversity status of pregnant mothers has significant effect on the incidence of anemia and key pregnancy outcomes in resource limited settings, like rural Ethiopia. Therefore, apart from the ongoing routine IFA supplementation, special emphasis should be given to dietary diversity of mothers to improve related outcomes of pregnancy and maternal health.

Keywords: anemia, birth weight, dietary diversity, pregnancy, pregnancy outcome

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Authors: Mira Kaneva

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The ongoing migration crisis polemic opens up the debate to the ambivalent essence of borders due to both the legality and legitimacy of the displacement of vast masses of people across the European continent. In neoliberal terms, migration is seen as an economic opportunity, or, on the opposite, as a social disparity; in realist terms, it is regarded as a security threat that calls for mobilization; from a critical standpoint, it is a matter of discourse on democratic governance. This paper sets the objective of analyzing borders through the Foucauldian prism of biopolitics. It aims at defining the specifics of the management of the human body by producing both the irregular migrant as a subject (but prevalently as an object in the discourse) and the political subjectivity by exercising state power in repressive practices, including hate speech. The study relies on the conceptual framework of Bigo, Agamben, Huysmans, among others, and applies the methodology of qualitative comparative analysis between the cases of borders (fences, enclaves, camps and other forms of abnormal spatiality) in Italy, Spain, Greece, the Republic of Macedonia, Serbia and Bulgaria. The paper thus tries to throw light on these cross- and intra-regional contexts that share certain similarities and differences. It tries to argue that the governmentality of the masses of refugees and economic immigrants through the speech acts of their exclusion leads to a temporary populist backlash; a tentative finding is that the status-quo in terms of social and economic measures remains relatively balanced, whereas, values such as freedom, openness, and tolerance are consecutively marginalized.

Keywords: Balkans, biopolitical borders, cross- and intra-regional discourse analysis, irregular migration, Mediterranean Europe, securitization vs. humanitarianism

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Authors: Briony Gray, Glenn Simpson, Hajira Dambha-Miller, Andrew Farmer

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Multimorbidity may be strongly affected by a variety of conditions, factors, and variables requiring higher demands on health and social care services, infrastructure, and expenses. Holding one or more conditions increases one’s risk for development of future conditions; with patients over 65 years old at highest risk. Psychosocial factors such as anxiety and depression are rising exponentially globally, which has been amplified by the COVID19 pandemic. These are highly correlated and predict poorer outcomes when held in coexistence and increase the likelihood of comorbid physical health conditions. While possible future reform of social and healthcare systems may help to alleviate some of these mounting pressures, there remains an urgent need to better understand the potential role health behaviours and psychosocial conditions - such as anxiety and depression – may have on aging populations. Using the UK healthcare scene as a lens for analysis, this study uses big data collected in the UK Longitudinal Study of Aging (ELSA) to examine the role of anxiety and depression in ageing populations (65yrs+). Using logistic regression modelling, results identify the 10 most significant variables correlated with both anxiety and depression from data categorised into the areas of health behaviour, psychosocial, socioeconomic, and life satisfaction (each demonstrated through literature review to be of significance). These are compared with wider global research findings with the aim of better understanding the areas in which social and healthcare reform can support multimorbidity interventions, making suggestions for improved patient-centred care. Scope of future research is outlined, which includes analysis of 59 total multimorbidity variables from the ELSA dataset, going beyond anxiety and depression.

Keywords: multimorbidity, health behaviours, patient centred care, psychosocial factors

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Authors: Elisavet Kechagia

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Due to the interplay of different genetic and environmental risk factors and its heterogeneous nature, the concept of attention deficit hyperactivity disorder (ADHD) has shaped controversy and conflicts, which have been, in turn, reflected in the controversial arguments about its treatment. Taking into account recent well evidence-based researches suggesting that ADHD is a condition, in which biopsychosocial factors are all weaved together, the current paper explores the multiple risk-factors that are likely to influence ADHD, with a particular focus on adolescents with ADHD who might experience comorbid social, emotional and behavioural disorders (SEBD). In the first section of this paper, the primary objective was to investigate the conflicting ideas regarding the definition, diagnosis and treatment of ADHD at an international level as well as to critically examine and identify the limitations of the two most prevailing sets of diagnostic criteria that inform current diagnosis, the American Psychiatric Association’s (APA) diagnostic scheme, DSM-V, and the World Health Organisation’s (WHO) classification of diseases, ICD-10. Taking into consideration the findings of current longitudinal studies on ADHD association with high rates of comorbid conditions and social dysfunction, in the second section the author moves towards an investigation of the transitional points −physical, psychological and social ones− that students with ADHD might experience during early adolescence, as informed by neuroscience and developmental contextualism theory. The third section is an exploration of the different perspectives of ADHD as reflected in individuals’ with ADHD self-reports and the KENT project’s findings on school staff’s attitudes and practices. In the last section, given the high rates of SEBDs in adolescents with ADHD, it is examined how cognitive behavioural therapy (CBT), coupled with other interventions, could be effective in ameliorating anti-social behaviours and/or other emotional and behavioral difficulties of students with ADHD. The findings of a range of randomised control studies indicate that CBT might have positive outcomes in adolescents with multiple behavioural problems, hence it is suggested to be considered both in schools and other community settings. Finally, taking into account the heterogeneous nature of ADHD, the different biopsychosocial and environmental risk factors that take place during adolescence and the discourse and practices concerning ADHD and SEBD, it is suggested how it might be possible to make sense of and meaningful improvements to the education of adolescents with ADHD within a multi-modal and multi-disciplinary whole-school approach that addresses the multiple problems that not only students with ADHD but also their peers might experience. Further research that would be based on more large-scale controls and would investigate the effectiveness of various interventions, as well as the profiles of those students who have benefited from particular approaches and those who have not, will generate further evidence concerning the psychoeducation of adolescents with ADHD allowing for generalised conclusions to be drawn.

Keywords: adolescence, attention deficit hyperctivity disorder, cognitive behavioural theory, comorbid social emotional behavioural disorders, treatment

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Authors: Malaw Ndiaye, Karim Konate

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Blockchain and smart contracts can be used to facilitate almost any financial transaction. Thanks to these smart contracts, the settlement of dividends and coupons could be automated. The blockchain would allow all these transactions to be saved in a single ledger rather than in many databases through many organizations as is currently the case. Smart contracts have become lucrative and profitable targets for attackers because they can hold a large amount of money. This paper takes stock of cryptocurrency crime by assessing attacks due to smart contracts and the cost of losses. These losses are often the result of two types of malicious contracts: vulnerable contracts and criminal smart contracts. Studying the behavior of malicious contracts allows us to understand the root causes and consequences of attacks and the defense capabilities that exist although they do not definitively solve the crime problem. It makes it possible to approach new defense perspectives which will be concretized in future work.

Keywords: blockchain, malicious smart contracts, crypto-currency, crimes, attacks

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Authors: Samira Boussema, Ben Hamed Salah

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Entrepreneurship was always considered to be the most appropriate remedy for various economies’ symptoms. It is presented as a complex process that faces several barriers thereby inhibiting a project’s implementation phase. In fact, after a careful review of the literature, we noticed that empirical researches on reasons behind non-developing entrepreneurial projects are very rare, suggesting a lack in modeling the process in general and the pre-start phase in particular. Therefore, in this study we try to identify the main environmental barriers to developing business projects in Tunisia through the study of a representative sample of undeveloped projects. To this end, we used a quantitative approach which allowed us to examine the various barriers encountered by young entrepreneurs during their projects’ implementation. Indeed, by modeling the phenomenon we found that these managers face barriers of legal, financial, educational and government support dimensions.

Keywords: entrepreneurship, environmental barriers, non-implementation of projects, structural modeling

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Authors: Sascha Kraus, Wolfgang Hora, Philipp Stieg, Thomas Niemand, Ferdinand Thies, Matthias Filser

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In most countries, small and medium-sized enterprises (SME) are the backbone of the economy due to their impact on job creation, innovation and wealth creation. Moreover, the ongoing globalization makes it inevitable – even for SME that traditionally focused on their domestic markets – to internationalize their business activities to realize further growth and survive in international markets. Thus, internationalization has become one of the most common growth strategies for SME and has received increasing scholarly attention over the last two decades. One the downside internationalization can be also regarded as the most complex strategy that a firm can undertake. Particularly for family firms, that are often characterized by limited financial capital, a risk-averse nature and limited growth aspirations, it could be argued that family firms are more likely to face greater challenges when taking the pathway to internationalization. Especially the triangulation of family, ownership, and management (so-called ‘familiness’) manifests in a unique behavior and decision-making process which is often characterized by the importance given to noneconomic goals and distinguishes a family firm from other businesses. Taking this into account, the concept of socio-emotional wealth (SEW) has been evolved to describe the behavior of family firms. In order to investigate how different internal and external firm characteristics shape internationalization success of family firms, we drew on a sample consisting of 297 small and medium-sized family firms from Germany, Austria, Switzerland, and Liechtenstein. Thus, we include SEW as essential family firm characteristic and added the two major intra-organizational characteristics, entrepreneurial orientation (EO), absorptive capacity (AC) as well as collaboration intensity (CI) and relational knowledge (RK) as two major external network characteristics. Based on previous research we assume that these characteristics are important to explain internationalization success of family firm SME. Regarding the data analysis, we applied a Fuzzy Set Qualitative Comparative Analysis (fsQCA), an approach that allows identifying configurations of firm characteristics, specifically used to study complex causal relationships where traditional regression techniques reach their limits. Results indicate that several combinations of these family firm characteristics can lead to international success, with no permanently required key characteristic. Instead, there are many roads to walk down for family firms to achieve internationalization success. Consequently, our data states that family owned SME are heterogeneous and internationalization is a complex and dynamic process. Results further show that network related characteristics occur in all sets, thus represent an essential element in the internationalization process of family owned SME. The contribution of our study is twofold, as we investigate different forms of international expansion for family firms and how to improve them. First, we are able to broaden the understanding of the intersection between family firm and SME internationalization with respect to major intra-organizational and network-related variables. Second, from a practical perspective, we offer family firm owners a basis for setting up internal capabilities to achieve international success.

Keywords: entrepreneurial orientation, family firm, fsQCA, internationalization, socio-emotional wealth

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Authors: William Sigvardsson, Christoffer Alenius, Jenny Lindblom, Andreas Johansson, Marcus Sandberg

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This article covers a study focusing on a subarctic greenhouse located in Nikkala, Sweden. Through a visit and the creation of a CFD model, the study investigates the differences in energy demand with high pressure sodium (HPS) lights and light emitting diode (LED) lights in combination with an air-carried and water-carried heating system accordingly. Through an IDA ICE model, the impact of insulating the parts of the greenhouse without active cultivation was also investigated. This, with the purpose of comparing the current system in the greenhouse to state-of-the-art alternatives and evaluating if an investment in either a water-carried heating system in combination with LED lights and insulating the non-cultivating parts of the greenhouse could be considered profitable. Operating a greenhouse in the harsh subarctic climate found in the northern parts of Sweden is not an easy task and especially if the operation is year-round. With an average temperature of under -5 °C from November through January, efficient growing techniques are a must to ensure a profitable business. Today the most crucial parts of a greenhouse are the heating system, lighting system, dehumidifying measures, as well as thermal screen, and the impact of a poorly designed system in a sub-arctic could be devastating as the margins are slim. The greenhouse studied uses a pellet burner to power their air- carried heating system which is used. The simulations found the resulting savings amounted to just under 14 800 SEK monthly or 18 % of the total cost of energy by implementing the water-carrying heating system in combination with the LED lamps. Given this, a payback period of 3-9 years could be expected given different scenarios, including specific time periods, financial aids, and the resale price of the current system. The insulation of the non-cultivating parts of the greenhouse was found to have possible savings of 25 300 SEK annually or 46 % of the current heat demand resulting in a payback period of just over 1-2 years. Given the possible energy savings, a reduction in emitted CO2 equivalents of almost 1,9 tonnes could be achieved annually. It was concluded that relatively inexpensive investments in modern greenhouse equipment could make a significant contribution to reducing the energy consumption of the greenhouse resulting in a more competitive business environment for sub-arctic greenhouse owners. New parts of the greenhouse should be built with the water-carried heating system in combination with state-of-the-art LED lights, and all parts which are not housing active cultivation should be insulated. If the greenhouse in Nikkala is eligible for financial aid or finds a resale value in the current system, an investment should be made in a new water-carried heating system in combination with LED lights.

Keywords: energy efficiency, sub-arctic greenhouses, energy measures, greenhouse climate control, greenhouse technology, CFD

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Authors: Lawong Damian Bernsah

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Neglected Tropical Diseases (NTDs) are most predominant among the poor and rural populations and are endemic in 149 countries. These diseases are the most prevalent and responsible for infecting 1.4 billion people worldwide. There are 17 neglected tropical diseases recognized by WHO that constitute the fourth largest disease health and economic burden of all communicable diseases. Five of these 17 diseases are considered for the cost analysis of this paper: lymphatic filariasis, onchocerciasis, trachoma, schistosomiasis, and soil transmitted helminth infections. WHO has proposed a roadmap for eradication and elimination by 2020 and treatments have been donated through the London Declaration by pharmaceutical manufacturers. The paper estimates the cost of NTD control programme and elimination for each NTD disease and total in Nigeria. This is necessary as it forms the bases upon which programme budget and expenditure could be based. Again, given the opportunity cost the resources for NTD face it is necessary to estimate the cost so as to provide bases for comparison. Cost of NTDs control and elimination programme is estimated using the population at risk for each NTD diseases and for the total. The population at risk is gotten from the national master plan for the 2015 - 2020, while the cost per person was gotten for similar studies conducted in similar settings and ranges from US$0.1 to US$0.5 for Mass Administration of Medicine (MAM) and between US$1 to US$1.5 for each NTD disease. The combined cost for all the NTDs was estimated to be US$634.88 million for the period 2015-2020 and US$1.9 billion for each NTD disease for the same period. For the purpose of sensitivity analysis and for robustness of the analysis the cost per person was varied and all were still high. Given that health expenditure for Nigeria (% of GDP) averages 3.5% for the period 1995-2014, it is very clear that efforts have to be made to improve allocation to the health sector in general which is hoped could trickle to NTDs control and elimination. Thus, the government and the donor partners would need to step-up budgetary allocation and also to be aware of the costs of NTD control and elimination programme since they have alternative uses. Key Words: Neglected Tropical Disease, Cost Analysis, NTD Programme Control and Elimination, Cost per Person

Keywords: Neglected Tropical Disease, Cost Analysis, Neglected Tropical Disease Programme Control and Elimination, Cost per Person

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Authors: Najade Sheriff, Malaz Elsaddig, Kevin Jones

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Background: Death in the first month of life accounts for an increasing proportion of under-five mortality. Advancement to reduce this number is being made across the globe; however, progress is slowest in sub-Saharan Africa. Objectives: The study aims to identify differences between neonatal deaths of inpatient babies born in a hospital facility in rural Uganda to those of neonates admitted from the community and to explore whether they can be used to risk stratify neonatal admissions. Results: A retrospective chart review was conducted on records for neonates admitted to the Special Care Baby Unit (SCBU) Kitovu Hospital from 1st July 2016 to 21st July 2017. A total of 442 babies were admitted and the overall neonatal mortality was 24.8% (40% inpatient, 37% community, 23% hospital referrals). 40% of deaths occurred within 24 hours of admission and the majority were male (63%). 43% of babies were hypothermic upon admission, a significantly greater proportion of which were inpatient babies born in labour ward (P=0.0025). Intrapartum related death accounted for ½ of all inpatient babies whereas complications of prematurity were the predominant cause of death in the community group (37%). Severe infection does not seem like a significant factor of mortality for inpatients (2%) as it does for community admissions (29%). Furthermore, with 52.5% of community admissions weighing < 1500g, very low birth weight (VLBW) may be a significant risk factor for community neonatal death. Conclusion: The neonatal mortality rate in this study is high, and the leading causes of death are all largely preventable. A high rate of inpatient birth asphyxiation indicates the need for good quality facility-based perinatal care as well as a greater focus on the management of hypothermia, such as Kangaroo care. Moreover, a reduction in preterm deliveries is necessary to reduce associated comorbidities, and monitoring for signs of infection is especially important for community admissions.

Keywords: community, mortality, newborn, Uganda

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Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

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Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

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Authors: Ruqaiya Khalil, Saman Usmani, Zaheer Ul-Haq

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The accurate characterization of ligand binding affinity is indispensable for designing molecules with optimized binding affinity. Computational tools help in many directions to predict quantitative correlations between protein-ligand structure and their binding affinities. Molecular dynamics (MD) simulation is a modern state-of-the-art technique to evaluate the underlying basis of ligand-protein interactions by characterizing dynamic and energetic properties during the event. Autoimmune diseases arise from an abnormal immune response of the body against own tissues. The current regimen for the described condition is limited to immune-modulators having compromised pharmacodynamics and pharmacokinetics profiles. One of the key player mediating immunity and tolerance, thus invoking autoimmunity is Interleukin-2; a cytokine influencing the growth of T cells. Molecular dynamics simulation techniques are applied to seek insight into the inhibitory mechanisms of newly synthesized compounds that manifested immunosuppressant potentials during in silico pipeline. In addition to estimation of free energies associated with ligand binding, MD simulation yielded us a great deal of information about ligand-macromolecule interactions to evaluate the pattern of interactions and the molecular basis of inhibition. The present study is a continuum of our efforts to identify interleukin-2 inhibitors of both natural and synthetic origin. Herein, we report molecular dynamics simulation studies of Interluekin-2 complexed with different antagonists previously reported by our group. The study of protein-ligand dynamics enabled us to gain a better understanding of the contribution of different active site residues in ligand binding. The results of the study will be used as the guide to rationalize the fragment based synthesis of drug-like interleukin-2 inhibitors as immune-modulators.

Keywords: immuno-modulators, MD simulation, protein-ligand interaction, structure-based drug design

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